Anhydrous hydrogel composition and delivery system

ABSTRACT

The present disclosure relates to anhydrous hydrogels useful as mucoadhesive (oral compositions) or as topical agents and may be used to deliver an active agent such as active pharmaceutical agents (API&#39;s), coagulants, fragrances, flavors, and other actives and excipients.

FIELD

The aspects of the present disclosure relates to anhydrous hydrogelsuseful as mucoadhesive (oral compositions) or as topical agents and maybe used to deliver an active agent such as active pharmaceutical agents(API's), coagulants, fragrances, flavors, and other actives andexcipients.

BACKGROUND

Hydrogels refer to a network of hydrophilic polymer chains that aregenerally found as a colloidal gel in which water is the dispersionmedium. Hydrogels are highly absorbent (they can contain over 99.9%water) natural or synthetic polymers. Hydrogels also possess a degree offlexibility very similar to natural tissue, due to their significantwater content (“Terminology of polymers and polymerization processes indispersed systems (IUPAC Recommendations 2011)”. Pure and AppliedChemistry 83 (12): 2229-2259. 2011). Common uses for hydrogels include:tissue engineering, sustained-release drug delivery systems, sensors(including biosensors), disposable diapers or sanitary napkins, contactlenses, and dressings for healing of burn or other wounds.

Hydrogels are characterized by the inclusion of water which acts todisperse the polymer into a colloidal mass. Unfortunately, the presenceof water limits the utility of these products to water sensitivematerials or environments where moisture is contraindicated. Thephysical properties of water also dictate the physical properties of thehydrogel, such as reactivity to acids and bases. Thus there is a need toidentify new hydrogels without the aqueous limitations.

SUMMARY

The aspects of the present disclosure relate to an anhydrous hydrogelfor the delivery of an active agent(s). Particularly important activeagents are those that are moisture sensitive. The aspects of the presentdisclosure also relate to processes for the preparation of,intermediates used in the preparation of, compositions (e.g.,pharmaceutical, medical device cosmetic, industrial) containing and theuses of such hydrogels in the treatment of disorders or application ofspecified agents to a surface.

One specific embodiment of the present disclosure relates tocompositions comprising an active agent (including acceptable saltthereof) pharmaceutical composition. Accordingly, in one embodiment, thepresent disclosure relates to a pharmaceutical composition comprising anactive agent, a pharmaceutically acceptable carrier and, optionally,additional medicinal or pharmaceutical agent(s).

Hydrogels are formed by combining a biocompatible polymer with apolyalcohol followed by the addition of an energy source such as heat orradiation. The hydrogels of the present disclosure do not dry out orchange shape upon standing. They are also resistant to so called “coldcreep” upon standing.

Suitable biocompatible polymers include sodium carboxymethylcellulose,pectin, sodium alginate, sodium/calcium alginate, polylactic acid,chitosan, carageenan, xanthan, gellan, polyaspartic acid, polyglutamicacid, hyaluronic acid or salts or derivatives thereof. Most preferred issodium carboxymethylcellulose.

Polyalcohols include alcohols containing 2 to 10 carbon atoms and 2 to 7hydroxyl groups including ethylene glycol, 1,2-propylene glycol,1,4-butylene glycol, glycerine, erythrit (meso-1,2,3,4-Butantetrol),sorbit, mannit, methylglucoside, diglycerine, triglycerine and/orpentaerythrit. Particularly, the polyol is glycerin.

Active agents include pharmaceutical agents such as analgesics,decongestants, bronchodilators and other antiasthmatic agents,cardiovascular agents such as beta-blockers, ACE inhibitors, diuretics,antithrombics, etc., diabetic agents, antihistamines, anesthetics,antifungals, antinauseants, antiemetics, antibacterial agents,antifungal agents, corticosteroids, neurological agents,anti-inflammatories, vaccines, biological agents (such as Humera, Enbreland Remicade), wound healing agents and anticonvulsants. Vitamins(particularly A, C, D and E) are a particular embodiment of an activeagent. The concentration of the active ingredient in the gel base is, ofcourse, dependent on the identity of the active agent, the condition andpatient being treated and the potency desired.

One group of particularly interesting active agents includepharmaceutical agents that are moisture sensitive such as biologicals,enzymes, proteins (and fragments thereof). Other moisture sensitivepharmaceutical agents include Adderall, alprazolam, gemifloxacin,hydromorphone and zolmitriptan.

Another embodiment relates to antifungal active agents such asAmphotericin B, Candicidin, Filipin, Hamycin, Natamycin, Nystatin,Rimocidin, Bifonazole, Butoconazole, Clotrimazole, Econazole,Fenticonazole, Isoconazole, Ketoconazole, Luliconazole, Miconazole,Omoconazole, Oxiconazole, Sertaconazole, Sulconazole, Tioconazole,Albaconazole, Fluconazole, Isavuconazole, Itraconazole, Posaconazole,Ravuconazole, Terconazole, Voriconazole, Abafungin, Amorolfin,Butenafine, Naftifine, Terbinafine, Anidulafungin, Caspofungin, andMicafungin.

Another embodiment of the present disclosure relates to wart removalcompounds such as salicylic acids. Such treatments are of specificinterest due to heightened response to the anhydrous medium of thehydrogel.

One specific embodiment relates to wound healing agents and products(such as gauze, bandage, and synthetic skin). Such agents include aloe,benzyl alcohol, coagulants (such as styptic, chitosan, vitamin K,phytomenadione, menadione, etamsylate, carbazochrome Batroxobin), ferricsulfate, ticosan, becaplermin, antimicrobial agents (includingantibiotics such as gentamycin, polymyxin B, zinc bacitracin,metronidazole, ofloxacin, minocycline, hydrocortisone, triamcinolone andtetracycline), antifungals, silver, povidone-iodine, polyhexamethylenebiguanide, dialkylcarbamoylchloride, lactoferrin, growth factors (suchas epidermal growth factor (EGF), platelet derived growth factor (PDGF),fibroblast growth factor (FGF), transforming growth factor (TGF-b1),insulin-like growth factor (IGF-1), human growth hormone, granulocytemacrophage colony stimulating (GM-CSF)).

Another embodiment relates to scar healing agents such as vitamins, aloevera, and benzyl alcohol.

Another embodiment of the present disclosure relates to active agents ofhemp oils, particularly CDB (or cannabidiol) and THC(tetrahydrocannabinol).

Active agents also includes cosmetic agents such as caffeine, sunscreens(such as butyl methoxydibenzoylmethane, oxybenzone, bumetrizole,ecamsule, phenylbenzimidazole sulfonic acid, ethylhexylmethoxycinnamate, menthyl anthranilate, octocrylene, para-aminobenzoicacid (PABA), and Tinosorb M), anti-inflammatories (such as salicylates),anti-acne agents (such as (isotretinoin, Benzamycin, clindamycin,Erythromycin, minocycline and tretinoin), vitamins (particularlyvitamins C and E, Biotin), ubiquinone, retinoids, Minoxidyl, Zincpyrithion, ketoconazole, allantoin, herbal extracts (such as PassionFruit extract (Passiflora Edulis), Red rose extract, Raspberry extract(Rubus Idaeus), Yucca herbal extract, Aloe vera leaf gel, Tea tree oil(Melaleuca Alternifolia), Peppermint leaf oil, Spearmint leaf oil,Wintergreen leaf oil (Gaultheria Procumbens), Lavender oil, Cinnamonleaf oil, Lemon peel oil, Valencia orange peel oil, Pink grapefruit peeloil, Roman chamomile oil (Anthemis Nobilis Flower Oil), and Jasmineoil), protein hydrolysates (i.e. short protein fragments that are stillcalled “peptides”) and skin lightening agents.

One particular cosmetic agent of interest is coenzyme Q10 (Co Q10), alsoknown as ubiquinone, ubidecarenone, coenzyme Q, and abbreviated at timesto CoQ10, CoQ or Q10. Ubiquinone is a 1,4-benzoquinone, where Q refersto the quinone chemical group, and 10 refers to the number of isoprenylchemical subunits in its tail.

Active agents also includes breath fresheners and oral hygienics such astriclosan, chlorhexidine gluconate and complexed metals such as Ag, Cu,Zn or Sn. Dental adhesives such as Gantrez MS-955 polymer (a mixedsodium and calcium salt of methyl vinyl ether and maleic anhydridecopolymer supplied as a powder) are also active agents. The formulationsof the present disclosure are particularly suitable as dental adhesivesdemonstrating significant holding power over other adhesivetechnologies. The formulations of the present disclosure are also usefulin the treatment of dry mouth and dry vagina syndromes.

Active agents also include odor reducing agents such as cyclodextrins,sodium bicarbonate, activated charcoal, potassium bicarbonate, zincundecylenate, undecylenic acid methyl ester, chlorophyll copper complex(CCC), Grillocin, bismuth compounds such as bismuth salicylate (BiS),bismuth subgallate (BiG) and bismuth citrate (BiC), and esters of3-methyl-2-hexenoic acid.

The hydrogels of the present disclosure are also useful ingredients indisposable diapers and feminine napkins. Ostomy bags and devices arealso important products benefiting from the odor reduction properties ofthe present hydrogels.

The hydrogels of the present disclosure are also useful for treatment ofnipple disorders, delivery of laxatives and anti-diarrheas such asloperamide and bismuth subsalicylate (such as Kaopectate andPepto-Bismol).

The hydrogels of the present disclosure are also useful as foodadditives which can preserve flavor and aroma.

Flavors and fragrances are well known in the food and cosmetic industry.Many of these compounds are susceptible to hydrolytic deactivation.Formulations of such flavor and fragrance compounds in the hydrogels ofthe present disclosure have surprising shelf life and release kinetics.

The formulations of the present disclosure are also useful sensors,electrodes and circuits. The use of these hydrogels in defibrillators isadvantageous due to the resilience of the actives in a non-aqueous base.

The formulations of the present disclosure are also useful in the fieldof veterinary medicine for the administration of active agents to petsand farm animals.

The formulations of the present disclosure are also useful as diagnostictools for the identification of infection, metal contamination andhumidity.

Another embodiment of the present disclosure relates to compositionsused as a rheology modifier for gel and liquid formulations.

A preferred embodiment of the present disclosure relates to an anhydroushydrogel composition comprising anhydrous glycerin, anhydrous sodiumcarboxymethyl cellulose and an active agent.

Glycerin (also commonly known as glycerol, glycerine, propanetriol and1,2,3-trihydroxypropane) is a widely used commercial product with over amillion tons produced annually. High purity glycerin (>99.5%) is known.Anyhdrous glycerin refers to glycerin with minimal residual water.United States Pharmacopeia (USP) describes one recognized standard ofhigh purity anhydrous glycerin (>99.0-101.0%) as containing not morethan 0.5% water. The otic therapeutic Auralgan is described ascontaining USP glycerin with not more than 0.6% water. The presentdisclosure includes such glycerin containing 0.5% and lower residualwater. Specific embodiments include 99.7% (weight) water free, 99.8%,99.9% and absolute (100%) (i.e. less than 0.3%, 0.2%, 0.1% residualwater).

Sodium carboxymethyl cellulose is a cellulose derivative withcarboxymethyl groups (—CH₂—CO₂H) bound to some of the hydroxyl groups ofthe glucopyranose monomers that make up the cellulose backbone.Commercial polymer products are typically categorized by averageglucopyranose chain length molecular weights (MW) of 70,000, 80,000,90,000 g/m. Anhydrous sodium carboxymethyl cellulose refers to a productwith minimal residual water.

The present inventors have surprisingly found that the combination ofanhydrous glycerin and sodium carboxymethyl cellulose (CMC) yields ananhydrous material that upon addition of heat (or radiation) istransformed into an anhydrous hydrogel. Unit dosage formulations may beprepared by the addition of 0.1 mg to 1 g of active agent (depending onthe active agent) with glycerin and CMC is likewise transformed into ahomogeneous hydrogel upon the addition of heat. These products have lessthan 0.5% water, more preferably less than 0.4% water, more preferablyless than 0.3% water.

Such anhydrous hydrogels are hygroscopic and thus may be subject to postproduction processes that maintain the product in a water-free state.One such method is coating of the hydrogel with a hydrophobic layer.Alternate methods include storage of products in moisture freecontainers. Many of the products once formed may be stable enough toatmospheric moisture such that they can be stored in standard deliveryapparatus.

Hydrogels of the present disclosure can be subjected to crosslinkingmethods which enhance the structure and function of the hydrogel.Suitable crosslinking chemical agents include divalent/multivalentmetallic cations (e.g., calcium, magnesium, zinc, copper, barium, iron,aluminium, chromium, cerium), phosphates (e.g., pentasodiumtripolyphosphate (TPP)), chromates (e.g., dipotassium dichromate),borates (e.g., sodium tetraborate decahydrate), peroxides (e.g., t-butylhydroperoxide), glycidyl(meth)acrylate, ethylene glycol diglycidylether, glutaraldehyde, glycerin, glycols, polyamidoamine epichlorohydrinresin, TMPTA, and the like, and mixtures thereof. Representativecrosslinking methods include thermogelation, ionotropic gelation,cryogelation, radiation-induced gelation, chemical gelation,coagulation, crystallization, vulcanization, curing, and combinationsthereof.

Another embodiment of the present disclosure relates to anhydroushydrogels additionally comprising multivalent metal ions (i.e. Ca++,Mg++, Fe+++, Zn++ etc) which may be used to modify the cohesive andsolubility characteristics as desired. So-called cross-linking resultingfrom multivalency makes the products more viscous and less hydrophilic.

Additional excipients include fillers such as fumed silica, calciumcarbonate, talc, corns starch, clays, methacrylate powder,polyethylene/polypropylene beads, etc.

The anhydrous hydrogels of the present disclosure may further comprise abuffer such as an acid such as citric acid, benzoic acid, salicylicacid, etc.; neutral buffers such as phosphate buffered saline etc.; oralkaline buffers such as borates etc. These buffering agents may be usedto adjust for pH sensitive applications.

In a preferable embodiment of the present disclosure, the hydrogelcomprises the biocompatible polymer (CMC) in an amount of 1 to about 50wt %, the polyalcohol (Glycerin) in an amount of 1 to about 20 wt %, andthe active agent is a medicinal herb extract in an amount of 1 to about30 wt % (unit dosage amounts include 0.1 mg to 1 g, more preferably 50mg to 750 mg of active).

The anhydrous hydrogels of the present disclosure generally comprise0.1-50% (w/w) of an anhydrous carboxymethyl cellulose such ascarboxymethyl cellulose, 99.5-50% anhydrous glycerin (w/w), and 0.1-50%of an active agent.

Another embodiment of the present disclosure relates to an anhydroushydrogel comprising from 5-30% NaCMC, 95-70% anhydrous glycerin and0.1-30% active agent.

Another embodiment of the present disclosure relates to an anhydroushydrogel comprising from 10-20% NaCMC, 90-80% anhydrous glycerin and0.1-30% active agent.

Another embodiment of the present disclosure relates to an anhydroushydrogel comprising from 14-16% NaCMC, 86-84% anhydrous glycerin and0.1-30% active agent.

Another embodiment of the present disclosure relates to a composition ofany of the aforesaid embodiments of hydrogel wherein said composition isin thin film, tablet, capsule, oral solution, or oral suspension dosageform.

Formulations suitable for oral administration include solid, semi-solidand liquid systems such as soft or hard capsules containing multi- ornano-particulates, liquids, or powders; lozenges (includingliquid-filled); chews; gels; fast dispersing dosage forms; films;ovules; sprays; and buccal/mucoadhesive patches.

The hydrogels of the present disclosure may also be administeredtopically, (intra)dermally, or transdermally to the skin or mucosa.Typical formulations for this purpose include gels, hydrogels, lotions,solutions, creams, ointments, dusting powders, dressings, foams, films,skin patches, wafers, implants, sponges, fibres, bandages andmicroemulsions. Liposomes may also be used. Typical carriers includealcohol, mineral oil, liquid petrolatum, white petrolatum, glycerin,polyethylene glycol and propylene glycol. Penetration enhancers may beincorporated—see, for example, J Pharm Sci, 88 (10), 955-958, by Finninand Morgan (October 1999).

Another embodiment of the present disclosure relates to an oralpharmaceutical preparation containing a therapeutically effective amountof an active agent or a salt thereof for once daily administration.

Another embodiment of the present disclosure relates to a compositioncontaining particles which have a core containing an active agent or asalt thereof coated with a barrier layer. The barrier layer is formedfrom a coating liquid that contains a least one water insoluble barrierforming component selected from a group consisting of ethyl cellulose,copolymers of acrylic and methacrylic esters and natural or syntheticwaxes, and a plasticizer.

The terms “treating” and “effective amount”, as used herein, unlessotherwise indicated, means reversing, alleviating, inhibiting theprogress of, or preventing the disorder or condition to which such termapplies, or one or more symptoms of such disorder or condition. The term“treatment”, as used herein, unless otherwise indicated, refers to theact of treating as “treating” is defined immediately above. The term“treating” also includes adjuvant and neo-adjuvant treatment of asubject.

Administration of the compounds of Formula I may be effected by anymethod that enables delivery of the compounds to the site of action.These methods include oral routes, intraduodenal routes, parenteralinjection (including intravenous, subcutaneous, intramuscular,intravascular or infusion), topical, and rectal administration.

The amount of the active agent administered will be dependent on thesubject being treated, the severity of the disorder or condition, therate of administration, the disposition of the compound and thediscretion of the prescribing physician. However, an effective dosage isin the range of about 0.001 to about 100 mg per kg body weight per day,preferably about 1 to about 35 mg/kg/day, in single or divided doses.For a 70 kg human, this would amount to about 0.05 to about 7 g/day,preferably about 0.1 to about 2.5 g/day. In some instances, dosagelevels below the lower limit of the aforesaid range may be more thanadequate, while in other cases still larger doses may be employedwithout causing any harmful side effect, provided that such larger dosesare first divided into several small doses for administration throughoutthe day.

As used herein, the term “combination therapy” refers to theadministration of an active agent together with an at least oneadditional pharmaceutical or medicinal agent, either sequentially orsimultaneously.

The present disclosure includes the use of a combination of an activeagent and one or more additional pharmaceutically active agent(s). If acombination of active agents is administered, then they may beadministered sequentially or simultaneously, in separate dosage forms orcombined in a single dosage form. Accordingly, the present disclosurealso includes pharmaceutical compositions comprising an amount of: (a) afirst agent comprising an active agent or a pharmaceutically acceptablesalt of the compound; (b) a second pharmaceutically active agent; and(c) a pharmaceutically acceptable carrier, vehicle or diluent.

In a further embodiment, a kit is disclosed. One example of such a kitis a kit including an injectable composition of a hydrogel. Another kitembodiment is a thin film adhesive.

These and other aspects and advantages of the exemplary embodiments willbecome apparent from the following detailed description. Additionalaspects and advantages of the present disclosure will be set forth inthe description that follows, and in part will be obvious from thedescription, or may be learned by practice of the present disclosure.Moreover, the aspects and advantages of the present disclosure may berealized and obtained by means of the instrumentalities and combinationsparticularly pointed out in the appended claims.

DETAILED DESCRIPTION OF THE PRESENT DISCLOSURE

The manufacture of the anhydrous hydrogels may be achieved using acoating line with a heat tunnel, coating a mixture of glycerin(anhydrous) with NaCMC (anhydrous) to a desired thickness and passingthe mixture through an oven (under suitable dry conditions so as toretain water free atmosphere) at 105° C. (min) for about 5 minutes (min)until mixture sets. The product may be extruded into molds or thinfilms. Active agents and additional components are either anhydrous ordehydrated before use. Subject mixture is treated to the same processingparameters as the coating line.

Preferably the composition is extruded directly onto a substrate such asa backing layer or release liner, and then pressed. The thickness of theresulting hydrogel-containing film, for most purposes, will be in therange of about 0.20 mm to about 0.80 mm, more usually in the range ofabout 0.37 mm to about 0.47 mm.

The hydrogel compositions of the present disclosure may be prepared bysolution casting, by admixing the glycerin and CMC at a concentrationtypically in the range of about 35% to 60% w/w followed by the additionof heat or radiation. The resulting solution is cast onto a substratesuch as a backing layer or release liner. Both admixture and casting arepreferably carried out at as low temperature as permitted. The substratecoated with the hydrogel film is then baked at a temperature in therange of about 80 degree C. to about 100 degree C., optimally about 90degree C., for time period in the range of about one to four hours,optimally about two hours.

An active agent may be delivered to a body surface by simply placing ahydrogel composition of the present disclosure on a body surface inactive agent-transmitting relation thereto. Alternatively, an activeagent-containing hydrogel composition may be incorporated into adelivery system or “patch.” In manufacturing such systems, the hydrogeladhesive composition may be cast or extruded onto a backing layer orrelease liner and will serve as the skin-contacting face of the systemand act as an active agent reservoir. Alternatively, the hydrogelcomposition may be used as an active agent reservoir within the interiorof such a system, with a conventional skin contact adhesive laminatedthereto to affix the system to a patient's body surface.

Optional ingredients include anti-oxidants, colorants, flavourings andflavour enhancers, preservatives, salivary stimulating agents, coolingagents, co-solvents (including oils), emollients, bulking agents,anti-foaming agents, surfactants and taste-masking agents.

Films in accordance with the present disclosure are typically preparedby evaporative drying of thin aqueous films coated onto a peelablebacking support or paper. This may be done in a drying oven or tunnel,typically a combined coater dryer, or by freeze-drying or vacuuming.

Solid formulations for oral administration may be formulated to beimmediate and/or modified release. Modified release formulations includedelayed-, sustained-, pulsed-, controlled-, targeted and programmedrelease.

Suitable modified release formulations for the purposes of the presentdisclosure may be adapted from those described in U.S. Pat. No.6,106,864. Details of other suitable release technologies such as highenergy dispersions and osmotic and coated particles are to be found inPharmaceutical Technology On-line, 25(2), 1-14, by Verma et al (2001).The use of chewing gum to achieve controlled release may be adapted fromthose described in WO 00/35298.

Systems for the topical, transdermal or transmucosal administration ofan active agent may comprise: a reservoir containing a therapeuticallyeffective amount of an active agent; an adhesive means for maintainingthe system in active agent transmitting relationship to a body surface;and a backing layer as described above, wherein a disposable releaseliner covers the otherwise exposed surface, protecting such surfaceduring storage and prior to use (also as described above).

The composition will contain a quantity of an active agent effective toprovide the desired dosage or effect over a predetermined deliveryperiod.

The compositions of the present disclosure may also include arate-controlling membrane on the body surface side of the drugreservoir. The materials used to form such a membrane are selected tolimit the flux of one or more components contained in the drugformulation, and the membrane may be either microporous or dense.Representative materials useful for forming rate-controlling membranesinclude polyolefins such as polyethylene and polypropylene, polyamides,polyesters, ethylene-ethacrylate copolymer, ethylene-vinyl acetatecopolymer, ethylene-vinyl methylacetate copolymer, ethylene-vinylethylacetate copolymer, ethylene-vinyl propylacetate copolymer,polyisoprene, polyacrylonitrile, ethylene-propylene copolymer,polysiloxane-polycarbonate block copolymer and the like.

The compositions of the present disclosure may also serve to deliver anactive agent using other routes of administration. For example, thecompositions may be formulated with excipients, carriers and the likesuitable for oral administration of an orally active drug. Thecompositions may also be used in buccal and sublingual drug delivery,insofar as the compositions can adhere well to moist surfaces within themouth. In buccal and sublingual systems, hydrolyzable and/or bioerodiblepolymers may be incorporated into the compositions to facilitate gradualerosion throughout a drug delivery period. Still other types offormulations and drug delivery platforms may be prepared using thepresent compositions, including implants, rectally administrablecompositions, vaginally administrable compositions, and the like.

Example 1

Using methods analogous to those described above the following anhydrousformulations were prepared.

Odor Control

Description A B C Glycerin (99.7%) 78.0 77.0 78.0 Sodium CMC 10.0 9.89.8 Zinc Oxide 0.0 0.8 0.8 Magnesium Oxide 0.0 0.5 0.5 PEG-40 HCO 10.010.0 10.0 Undecylenic 0.5 0.5 1.0 Acid Methyl Ester Fragrance 1.5 1.50.0 Total 100.0 100.0 100.0

Example 2

Dry Mouth

Description A B C Glycerin (99.7%) 74.00 78.00  78.00  Sodium CMC 18.00q.s. q.s. Coconut Oil 7.80 5.00 5.00 (for example) CoQ10 0.20 0.00 0.00Flouride 0.00 0.25-1.00 0.25-1.00 compound Flavor trace trace traceTotal 100.0 100.0   100.0  

Example 3

Food Thickener/Gravy

Description A B C Glycerin (99.7%) 69.00 70.00 75.00 Sodium CMC 20.0020.00 20.00 Anhydrous Coconut Oil 6.00 5.00 5.00 Dehydrated ChickenFlavor 5.00 0.00 0.00 Dehydrated Beef Flavor 0.00 5.00 0.00 Total 100.0100.0 100.0

Example 4

Denture Fixative Gel Film

Descrip- tion A B C D E Glycerin q.s. q.s. q.s. q.s. q.s. (99.7%) Sodium 20.00  20.00  20.00  20.00  20.00 CMC Ca(OH)₂ 0.140-2.54 0.140-2.54Mg(OH)₂ 0.100-1.82 0.100-1.82 Zn(OH)₂ 0.180-3.40 0.180-3.40 Trivalenttrace   0.00-trace cmpd.* Total 100.00 100.00 100.00 100.00 100.00

Example 5

API

Description A C Glycerin (99.7%) 78.00 80.00 Sodium CMC 17.00 20.00anhydrous Coconut Oil 5.00 0.00 (for example) API (e.g., etanercept)0.001-5.00% 0.001-5.00% Flavor trace trace Total 100.0 100.0

Example 6

Polymer-Polymer Complex Denture Adhesive Anhydrous Gel

Description A B C D Glycerin q.s. q.s. q.s. q.s. (99.7%) Sodium CMC20.00-50.00 20.00-50.00 20.00-50.00 20.00-50.00 Gantrez  1.00-30.00MS-955 (Ca—Na Salt) Polyvinyl-  1.00-20.00 pyrrolidinone (PVP) K90(anhydrous) Polyox 301  1.00-15.00 (anhydrous) Polyvinyl  1.00-20.00alcohol (PVOH) (anhydrous) TOTAL 100.00 100.00 100.00 100.00

An example of such a kit is a so-called blister pack. Blister packs arewell known in the packaging industry and are being widely used for thepackaging of pharmaceutical unit dosage forms (tablets, capsules, andthe like). Blister packs generally consist of a sheet of relativelystiff material covered with a foil of a preferably transparent plasticmaterial. During the packaging process recesses are formed in theplastic foil. The recesses have the size and shape of the tablets orcapsules to be packed. Next, the tablets or capsules are placed in therecesses and the sheet of relatively stiff material is sealed againstthe plastic foil at the face of the foil which is opposite from thedirection in which the recesses were formed. As a result, the tablets orcapsules are sealed in the recesses between the plastic foil and thesheet. Preferably the strength of the sheet is such that the tablets orcapsules can be removed from the blister pack by manually applyingpressure on the recesses whereby an opening is formed in the sheet atthe place of the recess. The tablet or capsule can then be removed viasaid opening.

All publications, including but not limited to, issued patents, patentapplications, and journal articles, cited in this application are eachherein incorporated by reference in their entirety.

Thus, while there have been shown, described and pointed out,fundamental novel features of the present disclosure as applied to theexemplary embodiments thereof, it will be understood that variousomissions and substitutions and changes in the form and details ofdevices and methods illustrated, and in their operation, may be made bythose skilled in the art without departing from the spirit or scope ofthe present disclosure. Moreover, it is expressly intended that allcombinations of those elements and/or method steps, which performsubstantially the same function in substantially the same way to achievethe same results, are within the scope of the present disclosure.Moreover, it should be recognized that structures and/or elements and/ormethod steps shown and/or described in connection with any disclosedform or embodiment of the present disclosure may be incorporated in anyother disclosed or described or suggested form or embodiment as ageneral matter of design choice. It is the intention, therefore, to belimited only as indicated by the scope of the claims appended hereto.

The invention claimed is:
 1. A composition, comprising: a. sodiumcarboxymethyl cellulose (NaCMC) in an amount of from 5% (w/w) to 30%(w/w), said sodium carboxymethyl cellulose including minimal residualwater; and b. anhydrous glycerine in an amount of from 70% (w/w) to 95%(w/w), wherein said composition is a solid or semi-solid gelcomposition.
 2. The composition according to claim 1, further includingan active agent in an amount of from 0.1% (w/w) to 30% (w/w).
 3. Thecomposition according to claim 2, wherein said active agent iscannabidiol (CBD).
 4. The composition according to claim 2, wherein saidactive agent is selected from cannabidiol (CBD) oil andtetrahydrocannabinol (THC) oil.
 5. The composition according to claim 1,wherein said anhydrous glycerin includes not more than 0.5% water. 6.The composition according to claim 2, wherein said active agent ismoisture sensitive.
 7. The composition according to claim 6, whereinsaid moisture sensitive active agent comprises pharmaceutical agentsincluding biologicals, enzymes, proteins and fragments thereof,Adderall, alprazolam, gemifloxacin, hydromorphone and zolmitriptan. 8.The composition according to claim 2 wherein said active agent is apharmaceutical agent selected from analgesics, decongestants,bronchodilators, antiasthmatic agents, cardiovascular agents, diabeticagents, antihistamines, anesthetics, antifungals, anti-nauseants,antiemetics, antibacterial agents, antifungal agents, corticosteroids,neurological agents, anti-inflammatories, vaccines, biological agents,wound healing agents, anticonvulsants and vitamins.
 9. The compositionaccording to claim 2 wherein said active agent is a wound healing agentselected from becaplermin, antimicrobial agents, silver,povidone-iodine, polyhexamethylene biguanide, dialkylcarbamoylchloride,lactoferrin, and growth factors.
 10. The composition according to claim2 wherein said active agent is a cosmetic agent.
 11. The compositionaccording to claim 10 wherein said active agent is the cosmetic agentubiquinone.
 12. The composition according to claim 2 wherein said activeagent is a dental adhesive.
 13. The composition according to claim 2wherein said solid or semi-solid gel composition comprises: a. sodiumcarboxymethyl cellulose (NaCMC) in an amount of from 10% (w/w) to 20%(w/w); b. anhydrous glycerin in an amount of from 80% (w/w) to 90%(w/w); and c. active agent in an amount of from 0.1% (w/w) to 30% (w/w).14. The composition according to claim 2 wherein said solid orsemi-solid gel composition comprises: a. sodium carboxymethyl cellulose(NaCMC) in an amount of from 14% (w/w) to 16% (w/w); b. anhydrousglycerin in an amount of from 84% (w/w) to 86% (w/w); and c. the activeagent in an amount of from 0.1% (w/w) to 30% (w/w).
 15. The compositionaccording to claim 2 wherein said solid or semi-solid gel composition isin unit dosage form.
 16. A composition, comprising: a. sodiumcarboxymethyl cellulose (NaCMC) in an amount of from 5% (w/w) to 30%(w/w), said sodium carboxymethyl cellulose including minimal residualwater; b. anhydrous glycerine in an amount of from 70% (w/w) to 95%(w/w); and c. cannabidiol (CBD) in an amount of from 0.1% (w/w) to 30%(w/w), wherein said composition is a solid or semi-solid gelcomposition.
 17. A method of preparing a composition comprising: a.mixing to homogeneity the following: i. sodium carboxymethyl cellulose(NaCMC) in an amount of from 5% (w/w) to 30% (w/w), said sodiumcarboxymethyl cellulose including minimal residual water; and ii.anhydrous glycerine in an amount of from 70% (w/w) to 95% (w/w); and b.adding sufficient energy to transform the mixture into a solid orsemi-solid gel composition.
 18. The method according to claim 17,wherein said mixing step further includes adding an active agent in anamount of from 0.1% (w/w) to 30% (w/w).
 19. The method according toclaim 17 wherein the energy source is heat.
 20. The method according toclaim 17 wherein the energy source is radiation.
 21. The methodaccording to claim 20 wherein the energy source is heat.
 22. The methodaccording to claim 18, wherein the active agent is cannabidiol (CBD).23. A kit comprising the composition of claim 1.